NM_183235.3:c.-23+4502C>T

Variant names:

• chr15-55265663-G-A
• rs8032594
• NM_183235.3:c.-23+4502C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_183235.3(RAB27A):​c.-23+4502C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.56 in 151,596 control chromosomes in the GnomAD database, including 25,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.56 (25040 hom., cov: 30)
• Consequence: RAB27A NM_183235.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 5 publications found

Genes affected

RAB27A (HGNC:9766): (RAB27A, member RAS oncogene family) The protein encoded by this gene belongs to the small GTPase superfamily, Rab family. The protein is membrane-bound and may be involved in protein transport and small GTPase mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. Alternative splicing occurs at this locus and four transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]

RAB27A Gene-Disease associations (from GenCC):

• Griscelli syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAB27A	NM_183235.3	c.-23+4502C>T		intron_variant	Intron 2 of 6	ENST00000336787.6	NP_899058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAB27A	ENST00000336787.6	c.-23+4502C>T		intron_variant	Intron 2 of 6	1	NM_183235.3	ENSP00000337761.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84788 AN: 151482 Hom.: 24984 Cov.: 30

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.491

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.746

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.535

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.560 AC: 84902 AN: 151596 Hom.: 25040 Cov.: 30 AF XY: 0.557 AC XY: 41206 AN XY: 74018

African (AFR) AF: 0.725 AC: 29987 AN: 41352

American (AMR) AF: 0.609 AC: 9289 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1844 AN: 3464

East Asian (EAS) AF: 0.746 AC: 3852 AN: 5164

South Asian (SAS) AF: 0.476 AC: 2278 AN: 4782

European-Finnish (FIN) AF: 0.417 AC: 4331 AN: 10390

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31618 AN: 67884

Other (OTH) AF: 0.533 AC: 1123 AN: 2106

Alfa AF: 0.526 Hom.: 3893

Bravo AF: 0.584

Asia WGS AF: 0.616 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8032594; hg19: chr15-55557861;